Get special offers, recipes, health news, PLUS our FREE seafood cooking guide!
Got it, thanks! Click here for your FREE seafood cooking guide & recipes e-booklet.
Food, Health, and Eco-news
Prozac-Type Drugs Proven No Better than Placebo
Analysis that included recently uncovered secret trials finds that SSRIs only match or barely beat the placebo effect 03/24/2008 By Craig Weatherby

After the solid one-two punch their products took in recent weeks, the makers of anti-depressant drugs probably feel like they need a Prozac.

Prozac, Zoloft, Paxil, and other members of the newest generation of anti-depressants are called selective serotonin re-uptake inhibitors or SSRIs.

Key Points

  • British team uncovers hidden studies; Inclusion in new analysis proves Prozac-type drugs work no better than placebo pills.
  • Findings follow recent discovery that drug makers published positive trials at a far higher rate than negative trials.
  • Nutritional factors deserve more research, based on positive preliminary findings.

SSRI-type drugs work by reducing the amount of serotonin – a neurotransmitter associated with mood maintenance – that is reabsorbed by neurons (brain cells) after being used to transmit signals across the electro-chemical bridges between them (synapses).

Thus, SSRIs indirectly increase the amount of serotonin available to brain cells.

Prozac and its pharmaceutical competitors take a fatal credibility blow

Just last month, we reported on the startling discovery by former FDA psychiatrist Erick H. Turner, M.D.

Dr. Turner found that  94 percent of anti-depressant trials with positive outcomes (i.e., effects superior to placebo pills) had been published, versus disclosure of only 14 percent of trials with negative or unclear results.

And according to the FDA's own study reviewers, the results of many of the “positive” studies were not as good as their authors claimed.

(For more on this, see “Major Heart and Mood Drugs Take Huge Credibility Hits.”)

Now the other shoe has dropped hard… right on the heads of drug makers, with distressing implications for people suffering from depression.

Hard on the heels of Dr. Turner's discovery, researchers in Britain used Freedom of Information requests to pry loose even more previously unpublished studies with primarily negative outcomes.

They pooled all of the previously unpublished (and largely negative) trials of SSRI-class drugs with the previously published (largely positive) trials.

The results were very different from those obtained by prior “meta-analyses,” which tended to support the efficacy of SSRIs like Prozac.

UK analysis proves devastating to Prozac and similar drugs
After including the clinical trials hidden by drug makers, British researchers at the University of Hull found that for most depression patients, Prozac-type anti-depressants produce no significant benefits, when compared with the effects of placebo pills.

The only exception to this rule is that minor, marginal benefits were detected among a small group of the most severely depressed patients.

And their analysis indicates that the slight benefits seen in some severely depressed patients stem from their relatively weak responses to the placebo effect, rather than any greater efficacy of SSRIs among this group.

Doctors urge cautious response
Psychiatrists say that patients taking SSRIs who become aware of this research should not stop taking their medication before consulting their doctor. 

If he or she agrees the pills are a waste, they will likely recommend a gradual, closely monitored withdrawal.

Some psychologists points out that if SSRIs provide a substantial placebo effect, this should not be discounted. But this advice presumes that a patient's drugs are cheap or cost free and produce no adverse side effects.

We take no pleasure in the failure of SSRIs drugs to exceed the benefits of placebo pills.

But we deplore the secretive sales strategies practiced by the makers of some SSRIs.

For example, in related news, New Scientist reported last month that US lawyers claim they've obtained documents suggesting that a skewed analysis of clinical trial data by GlaxoSmithKline researchers concealed suicide risks associated with Paxil (paroxetine) – for some 15 years.

These deceptions have led to false hopes, adverse effects – including weight gain, low libido, and mortal risks – and the waste of billions of dollars for prescriptions of dubious value.

Natural mood support

Needless to say, no one who feels depressed or shows signs of depression should self-diagnose or self-medicate without the guidance of a medical professional. (The signs include chronic anxiety, anger, and negative thoughts, and/or lack of energy and interest in people and normal pursuits.)

That said, it appears that it may be possible to enhance the brain's serotonin system, via two dietary approaches:

  • 5-HTP is the chemical our bodies use to construct serotonin (5-HT). And supplemental 5-HTP has shown some promise in animal studies and small, preliminary clinical trials, with fewer adverse effects than SSRIs (Shaw K et al. 2002). Much more clinical study is needed, however, to confirm the effects and define which classes of depressed persons may benefit most from 5-HTP.
  • Omega-3s are essential to the proper function of brain-cell membranes, and appear to support the serotonin system (Hibbeln JR et al. 1998). Among other effects, this could help explain the observed associations between higher omega-3 intakes and reduced risk of depression, as affirmed by the American Psychiatric Association's Committee on Research on Psychiatric Treatments (Freeman MP et al. 2006).

We'll keep you posted on developments… such as the logical but decidedly unlikely withdrawal of FDA approval for use of SSRIs in depression.

In truth, patients want "magic bullets," doctors want pills to prescribe, and US law affords no easy path to approval of non-patentable nutritional factors as medicines, no matter how much evidence of benefit may exist.


  • Freeman MP, Hibbeln JR, Wisner KL, Davis JM, Mischoulon D, Peet M, Keck PE Jr, Marangell LB, Richardson AJ, Lake J, Stoll AL. Omega-3 fatty acids: evidence basis for treatment and future research in psychiatry. J Clin Psychiatry. 2006 Dec;67(12):1954-67. Review.
  • Hibbeln JR, Linnoila M, Umhau JC, Rawlings R, George DT, Salem N Jr. Essential fatty acids predict metabolites of serotonin and dopamine in cerebrospinal fluid among healthy control subjects, and early- and late-onset alcoholics. Biol Psychiatry 1998; 44: 235-242.
  • Hibbeln JR. Seafood consumption and homicide mortality. A cross-national ecological analysis. World Rev Nutr Diet. 2001;88:41-6.Links
  • Shaw K, Turner J, Del Mar C.Are tryptophan and 5-hydroxytryptophan effective treatments for depression? A meta-analysis.Aust N Z J Psychiatry. 2002 Aug;36(4):488-91.
  • Shaw K, Turner J, Del Mar C.Tryptophan and 5-hydroxytryptophan for depression.Cochrane Database Syst Rev. 2002;(1):CD003198. Review.
  • Turner EH, Loftis JM, Blackwell AD. Serotonin a la carte: supplementation with the serotonin precursor 5-hydroxytryptophan.Pharmacol Ther. 2006 Mar;109(3):325-38. Epub 2005 Jul 14. Review.
  • Owen C, Rees AM, Parker G. The role of fatty acids in the development and treatment of mood disorders. Curr Opin Psychiatry. 2008 Jan;21(1):19-24.
  • Virkkunen ME, Horroboin DF, Jenkins DK, Manku MS: Plasma phospholipid essential fatty acids and prostaglandins in alcoholic, habitually violent and impulsive offenders. Biol Psychiatry 1987; 22: 1087-1096.